Regenerative medicine is one of the great biomedical challenges of this century, requiring research at the interface of the physical and life sciences as well as engineering. Cell-based therapies for tissue and organ regeneration will involve not only stem cell biology but also the crafting of bioactive matrices to support tissue growth. This will require cutting-edge supramolecular chemistry, nanotechnology, and microscale process engineering. Thus a central component of the proposed Center of Excellence in Translational Human Stem Cell Research at Northwestern University will be a Matrix Synthesis and Biomaterials Core. This core will develop novel synthetic scaffold materials for use in preclinical studies with human stem cells. These synthetic biomaterials will be made available to other investigators in the proposal, facilitating collaborative development of molecularly designed scaffolds for in vitro culture of human stem cells, as well as viable stem cell delivery strategies for cell-based therapeutics. Our technological hypothesis is that optimal regeneration of human tissues from stem cells will ultimately require molecular, nanoscale and microscale design of scaffold materials, which will have broad applicability to the treatment of a wide range of human diseases. Because less invasive delivery of scaffolds is desirable for clinical use, in situ self-assembly could be an important element of scaffold technologies. Thus scaffolds that can assemble themselves from simple liquid injections are desirable. Furthermore, artificial scaffolds for culturing human stem cells could eliminate the need to culture these cells on fetal animal cell layers, reducing the consequent barriers to human transplantation for cell-based therapeutics. By promoting differentiation into desired lineages, these scaffolds could also reduce the economic cost of such therapies, reducing the need for separation and purification of biological factors during expansion of progenitor cells. An iterative, discovery-driven process will be used to identify and then optimize scaffold materials to achieve the goals of this proposal, including the regeneration of central nervous system tissues and pancreatic islets.